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American Journal of Kidney Diseases :... Jun 2024Crystalglobulinemia is a rare syndrome characterized by intravascular crystallization of monoclonal immunoglobulins (MIgs). Data on kidney involvement are limited to...
RATIONALE & OBJECTIVE
Crystalglobulinemia is a rare syndrome characterized by intravascular crystallization of monoclonal immunoglobulins (MIgs). Data on kidney involvement are limited to case reports. This series characterizes the clinicopathologic spectrum of crystalglobulin-induced nephropathy (CIN).
STUDY DESIGN
Case series.
SETTING & PARTICIPANTS
Nineteen CIN cases were identified from the nephropathology archives of Mayo Clinic and Columbia University. CIN was defined by intravascular (extracellular) MIg crystals visible by light (LM) and electron microscopy (EM).
FINDINGS
Among the cases, 68% were male and 65% were Caucasian (median age 56 years). Most patients presented with severe AKI (median creatinine 3.5 mg/dL), hematuria, and mild proteinuria (median 1.1 g). Common extrarenal manifestations were constitutional (67%), cutaneous (56%), and rheumatologic (50%). Fifty percent of cases had hypocomplementemia. The hematologic disorders were monoclonal gammopathy of renal significance (MGRS) (72%), lymphoma (17%), or myeloma (11%), with 65% of these disorders discovered concomitantly with CIN. All patients had MIg identified on SPEP/SIF (IgGκ in 65%). The sFLC ratio was outside the renal range in 40%, and bone marrow biopsy detected the responsible clone in 67%. On LM, crystals involved glomeruli (100%) and vessels (47%), often with an inflammatory reaction (89%) and fibrin (58%). All cases exhibited crystal substructures (mostly paracrystalline) by EM. Immunofluorescence (IF) on paraffin embedded tissue was more sensitive than frozen tissue (92% versus 47%) for demonstrating the crystal composition (IgGκ in 63%). Follow up (median 20 months) was available in 16 patients. Eighty-one percent received steroids, 44% plasmapheresis, 38% hemodialysis, and 69% chemotherapy. Ninety-percent of patients who received clone-directed therapy achieved kidney recovery vs. 20% of those who did not (p=0.017).
LIMITATIONS
Retrospective design, small sample size.
CONCLUSIONS
CIN is a rare cause of nephropathy associated with lymphoplasmacytic disorders (mostly MGRS) and typically presents with severe AKI and extrarenal manifestations. Diagnosis often requires IF performed on paraffin embedded kidney tissue. Prompt initiation of clone-directed therapy, coupled with corticosteroids and plasmapheresis, may lead to recovery of kidney function.
PubMed: 38908425
DOI: 10.1053/j.ajkd.2024.04.019 -
Medicina 2024Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome in adults (20-30%). Light microscopy shows thickening of glomerular basement membrane...
INTRODUCTION
Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome in adults (20-30%). Light microscopy shows thickening of glomerular basement membrane with appearance of spikes. These histological findings are not evident in early forms, in which case the granular deposition pattern of IgG and/or C3 in the basement membrane by immunofluorescence (IF) constitutes the diagnostic tool that allows to differentiate it from minimal change disease (MCD). Complement system plays a key role in the pathophysiology of MN. C4d is a degradation product and a marker of the complement system activation. C4d labelling by immunohistochemical (HI) technique can help in the differential diagnosis between both glomerulopathies NM and MCD when the material for IF is insufficient and light microscopy is normal. Our objective was to explore the discrimination power of C4d to differentiate between MN and MCD in renal biopsy material.
METHODS
Paraffin-embedded samples were recovered from renal biopsies with a diagnosis of MN and MCD performed between 1/1/2008 and 4/1/2019. IH staining was performed by immunoperoxidase technique using a rabbit anti-human C4d polyclonal antibody.
RESULTS
In all cases with MN (n = 27, 15 males) with a median age of 63 (range: 18-87) years, C4d deposits were detected. In 21 cases with MCD (12 males) with a median age of 51 (range: 18-87) years, the C4d marking was negative in every samples.
CONCLUSION
The results indicate that the marking of the renal biopsy with C4d is a useful tool for the differential diagnosis between NM and MCD.
Topics: Glomerulonephritis, Membranous; Humans; Male; Adult; Middle Aged; Female; Aged; Complement C4b; Young Adult; Diagnosis, Differential; Aged, 80 and over; Adolescent; Biopsy; Biomarkers; Nephrosis, Lipoid; Peptide Fragments; Retrospective Studies
PubMed: 38907960
DOI: No ID Found -
Diagnostic Pathology Jun 2024Psoriasis is a disease of overactive immune system. OVOL1 and Filaggrin have been associated with many inflammatory skin lesions. To the best of our knowledge, the...
BACKGROUND
Psoriasis is a disease of overactive immune system. OVOL1 and Filaggrin have been associated with many inflammatory skin lesions. To the best of our knowledge, the correlation between OVOL1 and Filaggrin in psoriasis was not previously investigated. This work aims to search the immunohistochemical expression and correlation between OVOL1 and Filaggrin in psoriasis.
MATERIALS AND METHODS
Slides cut from paraffin blocks of 30 psoriasis cases and 30 control subjects were stained with OVOL1 and Filaggrin. Clinicopathological data were correlated with the results of staining.
RESULTS
OVOL1 and Filaggrin expression in epidermis showed a significant gradual reduction from normal skin to peri-lesional and psoriasis biopsies (P < 0.001). In contrast, psoriasis dermis showed a significant overexpression of OVOL1 in inflammatory cells in relation to peri-lesional biopsies (P < 0.002). OVOL1 demonstrated a significant direct correlation with Filaggrin expression in psoriasis (r = 0.568, P < 0.004). OVOL1 and Filaggrin expression in psoriasis skin epidermis demonstrated a statistically significant negative correlation with PASI score.
CONCLUSION
OVOL1 and Filaggrin might be involved in psoriasis-associated inflammation and skin hyperproliferation. OVOL1 might have a protective barrier function in the skin and could be used to stratify progressive disease. Filaggrin may play a role in progression of psoriasis. OVOL1 inhibition could be considered in suppression of Filaggrin function. OVOL1 agonists may be beneficial in psoriasis treatment.
Topics: Humans; Filaggrin Proteins; Psoriasis; Female; Intermediate Filament Proteins; Male; Immunohistochemistry; Adult; Middle Aged; Skin; Young Adult; Aged; Biomarkers; Case-Control Studies; Biopsy; Clinical Relevance; DNA-Binding Proteins; Transcription Factors
PubMed: 38907248
DOI: 10.1186/s13000-024-01491-4 -
Nefrologia Jun 2024There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the...
BACKGROUND
There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables.
MATERIAL AND METHODS
A retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16-65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed.
RESULTS
Twenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8 ± 18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (p = 0.035). A significant correlation was found between percentage of C4d expression in CG with SA (p = 0.012) and SA with tubular atrophy and interstitial fibrosis (p < 0.05).
CONCLUSIONS
C4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS.
PubMed: 38906767
DOI: 10.1016/j.nefroe.2023.04.007 -
Clinical Orthopaedics and Related... Jun 2024A liquid biopsy is a test that evaluates the status of a disease by analyzing a sample of bodily fluid, most commonly blood. In recent years, there has been progress in...
BACKGROUND
A liquid biopsy is a test that evaluates the status of a disease by analyzing a sample of bodily fluid, most commonly blood. In recent years, there has been progress in the development and clinical application of liquid biopsy methods to identify blood-based, tumor-specific biomarkers for many cancer types. However, the implementation of these technologies to aid in the treatment of patients who have a sarcoma remains behind other fields of cancer medicine. For this study, we chose to evaluate a sarcoma liquid biopsy based on circulating tumor DNA (ctDNA). All human beings have normal cell-free DNA (cfDNA) circulating in the blood. In contrast with cfDNA, ctDNA is genetic material present in the blood stream that is derived from a tumor. ctDNA carries the unique genomic fingerprint of the tumor with changes that are not present in normal circulating cfDNA. A successful ctDNA liquid biopsy must be able to target these tumor-specific genetic alterations. For instance, epidermal growth factor receptor (EGFR) mutations are common in lung cancers, and ctDNA liquid biopsies are currently in clinical use to evaluate the status of disease in patients who have a lung cancer by detecting EGFR mutations in the blood. As opposed to many carcinomas, sarcomas do not have common recurrent mutations that could serve as the foundation to a ctDNA liquid biopsy. However, many sarcomas have structural changes to their chromosomes, including gains and losses of portions or entire chromosomes, known as copy number alterations (CNAs), that could serve as a target for a ctDNA liquid biopsy. Murine double minute 2 (MDM2) amplification in select lipomatous tumors or parosteal osteosarcoma is an example of a CNA due to the presence of extra copies of a segment of the long arm of chromosome 12. Since a majority of sarcomas demonstrate a complex karyotype with numerous CNAs, a blood-based liquid biopsy strategy that searches for these CNAs may be able to detect the presence of sarcoma ctDNA. Whole-genome sequencing (WGS) is a next-generation sequencing technique that evaluates the entire genome. The depth of coverage of WGS refers to how detailed the sequencing is, like higher versus lower power on a microscope. WGS can be performed with high-depth sequencing (that is, > 60×), which can detect individual point mutations, or low-depth sequencing (that is, 0.1× to 5×), referred to as low-passage whole-genome sequencing (LP-WGS), which may not detect individual mutations but can detect structural chromosomal changes including gains and losses (that is, CNAs). While similar strategies have shown favorable early results for specific sarcoma subtypes, LP-WGS has not been evaluated for applicability to the broader population of patients who have a sarcoma.
QUESTIONS/PURPOSES
Does an LP-WGS liquid biopsy evaluating for CNAs detect ctDNA in plasma samples from patients who have sarcomas representing a variety of histologic subtypes?
METHODS
This was a retrospective study conducted at a community-based, tertiary referral center. Nine paired (plasma and formalin-fixed paraffin-embedded [FFPE] tissue) and four unpaired (plasma) specimens from patients who had a sarcoma were obtained from a commercial biospecimen bank. Three control specimens from individuals who did not have cancer were also obtained. The paired and unpaired specimens from patients who had a sarcoma represented a variety of sarcoma histologic subtypes. cfDNA was extracted, amplified, and quantified. Libraries were prepared, and LP-WGS was performed using a NextSeq 500 next-generation sequencing machine at a low depth of sequencing coverage (∼1×). The ichorCNA bioinformatics algorithm, which was designed to detect CNAs from low-depth genomic sequencing data, was used to analyze the data. In contrast with the gold standard for diagnosis in the form of histopathologic analysis of a tissue sample, this test does not discriminate between sarcoma subtypes but detects the presence of tumor-derived CNAs within the ctDNA in the blood that should not be present in a patient who does not have cancer. The liquid biopsy was positive for the detection of cancer if the ichorCNA algorithm detected the presence of ctDNA. The algorithm was also used to quantitatively estimate the percent ctDNA within the cfDNA. The concentration of ctDNA was then calculated from the percent ctDNA relative to the total concentration of cfDNA. The CNAs of the paired FFPE tissue and plasma samples were graphically visualized using aCNViewer software.
RESULTS
This LP-WGS liquid biopsy detected ctDNA in 9 of 13 of the plasma specimens from patients with a sarcoma. The other four samples from patients with a sarcoma and all serum specimens from patients without cancer had no detectable ctDNA. Of those 9 patients with positive liquid biopsy results, the percent ctDNA ranged from 6% to 11%, and calculated ctDNA quantities were 0.04 to 5.6 ng/mL, which are levels to be expected when ctDNA is detectable.
CONCLUSION
In this small pilot study, we were able to detect sarcoma ctDNA with an LP-WGS liquid biopsy searching for CNAs in the plasma of most patients who had a sarcoma representing a variety of histologic subtypes.
CLINICAL RELEVANCE
These results suggest that an LP-WGS liquid biopsy evaluating for CNAs to identify ctDNA may be more broadly applicable to the population of patients who have a sarcoma than previously reported in studies focusing on specific subtypes. Large prospective clinical trials that gather samples at multiple time points during the process of diagnosis, treatment, and surveillance will be needed to further assess whether this technique can be clinically useful. At our institution, we are in the process of developing a large prospective clinical trial for this purpose.
PubMed: 38905450
DOI: 10.1097/CORR.0000000000003161 -
Langmuir : the ACS Journal of Surfaces... Jun 2024The prevalence of icing in nature has become a significant threat to human work and life, prompting the development of more energy-efficient active/passive combination...
The prevalence of icing in nature has become a significant threat to human work and life, prompting the development of more energy-efficient active/passive combination anti-icing/deicing technologies. In order to overcome the disadvantage of the poor durability of superhydrophobic surfaces, lubricated surfaces inspired by nepenthes have been preferred. In this study, a paraffin and silicone oil-infused photothermal foam (PSIPF) with excellent overall performance was prepared using polypyrrole (PPy) as a photothermal conversion material, a mixture of silicone oil and paraffin as a lubricating fluid, and melamine foam (MF) as a carrier. The surface adhesive strength is less than 20 kPa at -20 °C, the melting time is only 1018 s at an irradiance of 200 W/m and -20 °C (0.2 sun), and surface droplets do not freeze within 1 h at -10 °C. Furthermore, the surface exhibits excellent mechanical durability and stability, maintaining optimal lubrication properties following repeated cycles of icing/deicing, water rinsing, and immersion for 2 days in acid and alkaline conditions. This photothermal lubricated surface with excellent anti-icing/deicing properties at low temperatures and in weak-light environments provides a wider range of applications for equipment at high latitudes and high altitudes.
PubMed: 38904776
DOI: 10.1021/acs.langmuir.4c01790 -
Frontiers in Endocrinology 2024Thyroid cancer rarely occurs in children and adolescents. Molecular markers such as , , and have been widely used in adult PTC. It is currently unclear whether these...
OBJECTIVES
Thyroid cancer rarely occurs in children and adolescents. Molecular markers such as , , and have been widely used in adult PTC. It is currently unclear whether these molecular markers have equivalent potential for application in pediatric patients. This study aims to explore the potential utility of a multi-gene conjoint analysis based on next-generation targeted sequencing for pediatric papillary thyroid carcinoma (PTC).
MATERIALS AND METHODS
The patients diagnosed with PTC (aged 18 years or younger) in the pediatrics department of Lishui District Hospital of Traditional Chinese Medicine were retrospectively screened. A targeted enrichment and sequencing analysis of 116 genes associated with thyroid cancer was performed on paraffin-embedded tumor tissues and paired paracancerous tissue of fifteen children (average age 14.60) and nine adults (average age 49.33) PTC patients. Demographic information, clinical indicators, ultrasonic imaging information and pathological data were collected. The Kendall correlation test was used to establish a correlation between molecular variations and clinical characteristics in pediatric patients.
RESULTS
A sample of 15 pediatric PTCs revealed a detection rate of 73.33% (11/15) for driver gene mutations and fusion. Compared to adult PTCs, the genetic mutation landscape of pediatric PTCs was more complex. Six mutant genes overlap between the two groups, and an additional seventeen unique mutant genes were identified only in pediatric PTCs. There was only one unique mutant gene in adult PTCs. The tumor diameter of pediatric PTCs tended to be less than 4cm (p<0.001), and the number of lymph node metastases was more than five (p<0.001). Mutations in specific genes unique to pediatric PTCs may contribute to the onset and progression of the disease by adversely affecting hormone synthesis, secretion, and action mechanisms, as well as the functioning of thyroid hormone signaling pathways. But, additional experiments are required to validate this hypothesis.
CONCLUSION
mutation and fusion are involved in the occurrence and development of adolescent PTC. For pediatric thyroid nodules that cannot be determined as benign or malignant by fine needle aspiration biopsy, multiple gene combination testing can provide a reference for personalized diagnosis and treatment by clinical physicians.
Topics: Humans; Female; Adolescent; Thyroid Cancer, Papillary; Male; Child; Thyroid Neoplasms; Mutation; Retrospective Studies; Proto-Oncogene Proteins B-raf; Adult; Middle Aged; Biomarkers, Tumor; Proto-Oncogene Proteins c-ret; High-Throughput Nucleotide Sequencing; DNA Mutational Analysis
PubMed: 38904052
DOI: 10.3389/fendo.2024.1405142 -
BMC Public Health Jun 2024Injury due to ingestion of harmful chemicals has become an area of concern globally. In South Africa, paraffin has been widely implicated in multiple health outcomes,...
BACKGROUND
Injury due to ingestion of harmful chemicals has become an area of concern globally. In South Africa, paraffin has been widely implicated in multiple health outcomes, including severe ingestion injuries. A specific category of such injuries is those that are self-inflicted. A significant proportion of self-inflicted ingestion is reported to be intentional, although intentionality for self-infliction may be difficult to determine. Nonetheless, the identification of key explanatory risks and demographic factors of self-inflicted ingestion may contribute towards a better understanding of self-inflicted and harmful chemical ingestion injuries.
METHODS
This study used secondary data that had been collected on burn injuries of all causes, including those due to the ingestion of harmful chemicals, from a sample of South Africans from low-income communities close to major metropolitan centres. The current analysis focused on the risks for self-inflicted ingestion injuries and used logistic regression to determine risks for self-inflicted ingestion as differentiated from ingestion due to the actions of another person (other-inflicted ingestion) by sex and age cohort of the victim, and the presence of alcohol, by examining paraffin ingestion versus that of other chemicals.
RESULTS
The overwhelming majority of ingestion injuries (92.1%) were self-inflicted. The current findings indicate that sex (with females almost twice as likely to present with self-inflicted ingestion), age cohort (with those aged 18-29 and 30-44 years old four times more likely affected than older adults), presence of alcohol (twice as likely present than amongst individuals reporting ingestion injuries inflicted by others), and chemicals other than paraffin (three times more likely) are key explanatory factors for an increased risk for self-inflicted ingestion of harmful chemicals.
CONCLUSIONS
The study empirically confirms the role of several key risk factors in what remains a relatively unreported and understudied phenomenon, but which appears to align with the demographic and risk profile reported for suicidal injuries through chemical ingestion, i.e. intentional self-inflicted ingestion. The findings may contribute towards improved safety policies on the availability and sale of chemical products and more focussed community interventions for at-risk individuals such as females and young people. It also flags the importance of assessing for alcohol use and alcohol use disorders at hospital admission of self-ingestion injuries.
Topics: Humans; Female; Male; Adolescent; South Africa; Adult; Self-Injurious Behavior; Risk Factors; Young Adult; Paraffin; Middle Aged; Burns
PubMed: 38902608
DOI: 10.1186/s12889-024-18971-3 -
NPJ Precision Oncology Jun 2024We conducted spatial immune tumor microenvironment (iTME) profiling using formalin-fixed paraffin-embedded (FFPE) samples of 25 KRAS-mutated non-small cell lung cancer...
We conducted spatial immune tumor microenvironment (iTME) profiling using formalin-fixed paraffin-embedded (FFPE) samples of 25 KRAS-mutated non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), including 12 responders and 13 non-responders. An eleven-marker panel (CD3, CD4, CD8, FOXP3, CD68, arginase-1, CD33, HLA-DR, pan-keratin (PanCK), PD-1, and PD-L1) was used to study the tumor and immune cell compositions. Spatial features at single cell level with cellular neighborhoods and fractal analysis were determined. Spatial features and different subgroups of CD68 cells and FOXP3 cells being associated with response or resistance to ICIs were also identified. In particular, CD68 cells, CD33 and FOXP3 cells were found to be associated with resistance. Interestingly, there was also significant association between non-nuclear expression of FOXP3 being resistant to ICIs. We identified CD68 cells in the lung cancer tissues being associated with improved responses, which should be insightful for future studies of tumor immunity.
PubMed: 38898200
DOI: 10.1038/s41698-024-00626-6 -
Scientific Reports Jun 2024The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the...
The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the virus is crucial. Our goal was to investigate the proteins present in the serum of patients with OPSCC, which were not previously studied in OPSCC tissue. We examined the difference in expression of these proteins between HPV-positive and -negative tumors and their correlation with clinicopathological parameters and patient survival. The study included 157 formalin-fixed, paraffin-embedded tissue samples and clinicopathological data. Based on the protein levels in the sera of OPSCC patients, we selected 12 proteins and studied their expression in HPV-negative and HPV-positive OPSCC cell lines. LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein´s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance. LRG1 expression was strong in HPV-negative whereas SDR16C5 expression was strong in HPV-positive tumors. Correlation was observed between LRG1, SDR16C5, and PIP4K2C expression and patient survival. High expression of PIP4K2C was found to be an independent prognostic factor for overall survival and expression correlated with HPV-positive tumor status. The data suggest the possible role of LRG1, SDR16C5 and PIP4K2C in OPSCC biology.
Topics: Humans; Male; Oropharyngeal Neoplasms; Female; Middle Aged; Aged; Papillomavirus Infections; Glycoproteins; Carcinoma, Squamous Cell; Biomarkers, Tumor; Squamous Cell Carcinoma of Head and Neck; Papillomaviridae; Adult; Prognosis; Cell Line, Tumor
PubMed: 38898137
DOI: 10.1038/s41598-024-64823-w